Hyperthermia has been widely investigated for use in tumor therapy, either as a sole treatment modality or as an adjunct to radiation or chemotherapy (references 1-4). Hyperthermia offers a number of potential advantages for cancer treatment. Studies have shown that tumor cells are more susceptible to destruction by heat, due in part to the relatively greater hypoxia and lower pH in solid tumors (references 5, 6). The restricted blood flow in solid tumors, especially larger ones, reduces the ability of tumors to dissipate heat (reference 7). Hyperthermia has been shown to enhance the sensitivity of tumors to radiation and to chemotherapeutic agents (reference 1, 8). The side effects of hyperthermia on normal tissue are insignificant at temperatures less than 41.8.degree. C., and hyperthermia can be used repeatedly without cumulative damage to normal tissue.
Despite its potential advantages, hyperthermic treatment of solid tumors has been found to provide rather limited selective tumor destruction heretofore. This limitation is due in part to the inability of hyperthermic treatment methods used in the prior art to produce a sufficient temperature differential between tumor and surrounding normal tissue, even though tumor tissue has a generally impaired ability to dissipate heat. Frequently at input energy levels which approach tolerance for normal tissues, there are areas within the tumor mass and along the more vascularized periphery which do not heat sufficiently (12).
Attempts to augment response to hyperthermic treatment by means of arterial clamping, have been reported (references 9-11). Occlusion of the regional artery supplying a tumor reduces the arterial pressure distal to the occlusion, which in theory has the potential for producing greater heat build-up in the clamped tumor tissue. In the studies reported, arterial clamping was, in fact, found to enhance the hyperthermic damage to tumor tissue. However, where heating patterns in clamped and unclamped tissue were examined, no differences were observed between tumor and adjacent normal tissues. The results suggest that the enhanced toxicity observed is related to metabolic effects of vaso-occlusion, rather than to differential heating. Therefore, arterial clamping, although beneficial, fails to provide a significant advantage in terms of temperature selectivity.
The desirability of creating a temperature differential in hyperthermic cancer treatment is related to the greater rate of tissue destruction which is known to occur at increasing tissue temperatures above about 42.degree. C. The general rule is that each degree increase in tissue temperature approximately halves the time required to produce a given amount of tissue damage. Thus if a given amount of tissue damage results from heating the tissue at 42.degree. C. for two hours, the same amount of damage is produced in an hour at 43.degree. C., and in one-half hour at 44.degree. C. Viewed another way, each one-degree increase in temperature differential can double the extent of selective tissue damage produced by heating the tissue for a given time.